【摘要】：糖尿病視網(wǎng)膜病變(diabetic retinopathy, DR)是糖尿病最常見(jiàn)的微血管并發(fā)癥之一,常見(jiàn)于糖尿病病程10年以上的患者,給患者的視力造成極大的威脅。作為目前的主要治療方法,激光治療廣泛應(yīng)用于臨床并獲得了肯定的療效。全視網(wǎng)膜光凝術(shù)(panretinal photocoagulation, PRP)通過(guò)破壞周邊部的視網(wǎng)膜而降低視網(wǎng)膜的氧耗,以保證后極部能得到充分的氧供。傳統(tǒng)的ETDRS (Early Treatment Diabetic Retinopathy Study)激光因激光能量較高、作用時(shí)間長(zhǎng)而對(duì)視網(wǎng)膜及脈絡(luò)膜造成一定損傷,術(shù)后患者發(fā)生黃斑水腫的概率增加。先進(jìn)的Pascal激光系統(tǒng)采用創(chuàng)新性的點(diǎn)陣式激光模式,且激光作用時(shí)間縮短為20毫秒,大大提高了治療效率,減輕了激光損傷。隨著光學(xué)相干斷層掃描(Optical Coherence Tomography, OCT)技術(shù)的飛速發(fā)展,其對(duì)于視網(wǎng)膜10層結(jié)構(gòu)的分辨已相當(dāng)清楚。近兩年出現(xiàn)的EDI (enhanced-depth imaging)技術(shù)使脈絡(luò)膜在OCT上清晰地顯示成為了可能。脈絡(luò)膜作為外層視網(wǎng)膜的主要血供來(lái)源,在DR這一類(lèi)視網(wǎng)膜血管性疾病中扮演了怎樣的角色呢?已有研究發(fā)現(xiàn)DR患者的脈絡(luò)膜較正常對(duì)照組變薄,那么激光治療前后脈絡(luò)膜的厚度是否會(huì)發(fā)生變化呢?這一變化是否與視力預(yù)后相關(guān)呢?這是本課題的核心研究所在。作為視網(wǎng)膜功能學(xué)和形態(tài)學(xué)的客觀評(píng)價(jià)工具,多焦視網(wǎng)膜電圖(multifocal electroretinography, mfERG)和OCT已被用于多種疾病的視力預(yù)后研究,包括糖尿病視網(wǎng)膜病變、糖尿病黃斑水腫等。但尚未見(jiàn)到關(guān)于PRP的相關(guān)報(bào)道,那么mfERG與OCT是否與DR行全視網(wǎng)膜光凝術(shù)的預(yù)后密切相關(guān)呢?這是本課題關(guān)注的另一重點(diǎn)。第一部分糖尿病視網(wǎng)膜病變?nèi)暰W(wǎng)膜光凝術(shù)前后脈絡(luò)膜厚度變化目的研究糖尿病視網(wǎng)膜病變?nèi)暰W(wǎng)膜光凝后黃斑區(qū)和光斑區(qū)脈絡(luò)膜厚度變化。方法本部分研究納入了34例需行全視網(wǎng)膜光凝的糖尿病視網(wǎng)膜病變患者(包括嚴(yán)重非增殖期糖尿病視網(wǎng)膜病變和早期增殖期糖尿病視網(wǎng)膜病變患者)。分別在基線(xiàn)、激光后1個(gè)月和激光后3個(gè)月,利用光學(xué)相干斷層掃描儀的EDI模式掃描了黃斑區(qū)和光斑區(qū)的脈絡(luò)膜厚度,并測(cè)量了患者的最佳矯正視力(best corrected visual acuity, BCVA)。結(jié)果黃斑區(qū)脈絡(luò)膜厚度基線(xiàn)為307.2±70.7μm,激光后1個(gè)月為318.0±76.4μm(P0.001),3個(gè)月為317.4±75.3μm(P0.001),脈絡(luò)膜厚度的增加具有統(tǒng)計(jì)學(xué)差異。而光斑區(qū)的脈絡(luò)膜厚度則從基線(xiàn)的227.5±45.0μm降至術(shù)后一個(gè)月的206.9±41.1μm(P0.001)和術(shù)后三個(gè)月的206.0±41.4μm(P0.001)。無(wú)論是在PRP術(shù)后一個(gè)月還是三個(gè)月,脈絡(luò)膜厚度的變化均與視力變化無(wú)關(guān)。在多元線(xiàn)性回歸分析中,僅PRP術(shù)前的視力和中心凹視網(wǎng)膜厚度與視力變化具有統(tǒng)計(jì)學(xué)意義的相關(guān)性。結(jié)論在嚴(yán)重NPDR和早期PDR患者中,黃斑區(qū)平均脈絡(luò)膜在PRP術(shù)后增加,而光斑區(qū)平均脈絡(luò)膜厚度則減少。這一結(jié)果可能提示了PRP術(shù)后脈絡(luò)膜血流的重新分布,對(duì)于保證視網(wǎng)膜的代謝至關(guān)重要。第二部分糖尿病視網(wǎng)膜病變?nèi)暰W(wǎng)膜光凝術(shù)預(yù)后相關(guān)因素分析目的研究mfERG和OCT在判斷糖尿病視網(wǎng)膜病變行全視網(wǎng)膜光凝術(shù)的預(yù)后中的價(jià)值。方法本部分研究納入了42例需行全視網(wǎng)膜光凝的糖尿病視網(wǎng)膜病變患者(包括嚴(yán)重非增殖期糖尿病視網(wǎng)膜病變和早期增殖期糖尿病視網(wǎng)膜病變患者)。在基線(xiàn)時(shí)進(jìn)行mfERG、OCT和BCVA的測(cè)量,并在PRP術(shù)后6個(gè)月再次測(cè)量BCVA。PRP術(shù)前的數(shù)據(jù)與術(shù)后6個(gè)月視力的關(guān)系采用了Pearson相關(guān)分析和多元線(xiàn)性回歸進(jìn)行分析。結(jié)果入選的42例患眼中,31例(73.8%)視力較術(shù)前提高或維持原狀,11例(26.2%)激光術(shù)后視力下降。在全部9個(gè)區(qū)域中,最終BCVA與mfERG振幅和潛伏期均密切相關(guān),且振幅與視力的相關(guān)性更顯著。中心凹層面光感受器細(xì)胞內(nèi)外節(jié)連接(photoreceptor inner and outer segment junction, IS/OS)和外界膜(external limiting membrane, ELM)連續(xù)性,以及大部分區(qū)域的視網(wǎng)膜厚度也與最終視力密切相關(guān)。在綜合以上多種因素的多元線(xiàn)性回歸模型中,中心區(qū)域的mfERG振幅、中心凹IS/OS連續(xù)性、患者PRP術(shù)前視力及患者年齡與最終BCVA的相關(guān)性具有統(tǒng)計(jì)學(xué)差異。在大部分區(qū)域,視網(wǎng)膜厚度也與mfERG振幅和潛伏期相關(guān),顳側(cè)和下方區(qū)域更明顯,特別是外環(huán)。結(jié)論mfERG的振幅偏低或中心凹IS/OS紊亂與PRP術(shù)后視力預(yù)后不良關(guān)系密切。綜上所述,本研究發(fā)現(xiàn)PRP術(shù)后黃斑區(qū)脈絡(luò)膜厚度增加而光斑區(qū)脈絡(luò)膜厚度減少,可能提示PRP引起了脈絡(luò)膜血流的重分布,盡管與視力變化無(wú)直接關(guān)系,但是視網(wǎng)膜代謝的保障。mfERG和OCT檢查所提供的視網(wǎng)膜結(jié)構(gòu)和功能兩方面信息均對(duì)PRP術(shù)后糖尿病視網(wǎng)膜病變患眼的視力預(yù)后有一定影響。其中,多焦視網(wǎng)膜電圖的振幅和中心凹IS/OS連續(xù)性是最有價(jià)值的預(yù)測(cè)指標(biāo)。
[Abstract]:Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is common in patients with more than 10 years of diabetes. As the current primary treatment method, laser treatment is widely used in clinic and has obtained positive curative effect. All-retinal photocoagulation (PRP) reduces the oxygen consumption of the retina by destroying the retina of the peripheral part, so as to ensure that the posterior pole part can be provided with sufficient oxygen. The traditional ETDRS (ETDRS) laser has high laser energy, long acting time and some damage to the retina and the choroid, and the probability of macular edema in the patients after operation is increased. The advanced Pascal laser system adopts an innovative lattice-type laser mode, and the laser action time is shortened to 20 milliseconds, so that the treatment efficiency is greatly improved, and laser damage is reduced. With the rapid development of optical coherence tomography (OCT), the resolution of the structure of the retina 10 layer is quite clear. In recent two years, the development of the EDI (advanced-depth imaging) technique has made it possible to clearly display the choroid in the OCT. Choroid, as the main source of blood supply of the outer retina, plays an important role in the DR type of retinal vascular disease? It has been found that the choroid of the DR patient is thinner than that of the normal control group, and the thickness of the choroid before and after laser treatment will change. Is this change related to the visual prognosis? This is the core research institute of the subject. As an objective evaluation tool for retinal function and morphology, multi-focal electroretinography (mfrERG) and OCT have been used in the study of visual outcomes for a variety of diseases, including diabetic retinopathy, diabetic macular edema, and the like. But if the relevant reports on PRP have not been seen, it is closely related to whether the mfERG and OCT are closely related to the prognosis of DR-line full-retinal photocoagulation? This is another focus of the subject's attention. The changes of the choroidal thickness in the macular area and the spot area after the full-retinal photocoagulation of the diabetic retinopathy were studied with the aim of the changes of the choroidal thickness before and after the whole-retinal photocoagulation of the first part of the diabetic retinopathy. Methods Thirty-four patients with diabetic retinopathy (including severe non-proliferative diabetic retinopathy and early proliferative diabetic retinopathy) were included in this part of the study. The choroidal thickness of the macular region and the spot region was scanned with the EDI pattern of the optical coherence tomography scanner and the best corrected visual acuity (BCVA) was measured at baseline,1 month after laser and 3 months after the laser. Results The baseline of the choroidal thickness in the macular region was 307.2-70.7. m u.m, the first month after the laser was 318.0-76.4. m (P 0.001), the third month was 317.4-75.3. m (P 0.001), and the increase of the choroidal thickness was statistically different. And the choroidal thickness of the spot area decreased from 227.5 to 45.0. m in the baseline to 206.9 to 41.1. m after the operation (P0.01) and 206.0 to 41.4. m in the first three months (P0.001). The changes in the choroidal thickness were not related to the visual change, either one month or three months after the PRP. In the multivariate linear regression analysis, only the pre-operative visual and central retinal thickness of the PRP had a statistically significant correlation with the visual change. Conclusion In the patients with severe NPDR and early PDR, the average choroid in the macular area is increased after the PRP, while the average choroidal thickness in the spot area is reduced. This result may suggest a re-distribution of the choroidal blood flow after the PRP operation, which is critical for ensuring the metabolism of the retina. Objective To study the value of mfERG and OCT in determining the prognosis of all-retinal photocoagulation in diabetic retinopathy. Methods A total of 42 diabetic retinopathy (including severe non-proliferative diabetic retinopathy and early proliferative diabetic retinopathy) were included in this part of the study. The measurements of the mfrERG, OCT and BCVA were performed at baseline and the BCVA was again measured 6 months after the PRP. The relationship between the pre-operation data of the PRP and the 6-month visual acuity was analyzed using Pearson correlation analysis and a multivariate linear regression. Results The visual acuity of 31 patients (73.8%) was improved or maintained in the eyes of 42 patients, and the visual acuity of 11 (26.2%) patients decreased after operation. In all 9 regions, the final BCVA was closely related to the amplitude and latency of the mfERG, and the correlation between the amplitude and the vision was more significant. The continuity of photoreceptors and outer segment junction (IS/ OS) and external membrane (ELM), as well as the retinal thickness in most of the regions, are also closely related to the final vision. In the multiple linear regression model with multiple factors, the mfERG amplitude, the central concave IS/ OS continuity, the pre-operative visual acuity of the patient and the correlation of the patient's age with the final BCVA were statistically different. In most area, that thickness of the retina is also relate to the amplitude and latency of the mfERG, and the upper and lower regions are more pronounced, in particular the outer ring. Conclusion The low amplitude of mfrERG or the disorder of the central concave IS/ OS is closely related to the poor prognosis of the vision after the operation of the PRP. In conclusion, in the present study, the choroidal thickness of the macular area after the PRP is increased and the choroidal thickness of the spot area is reduced, which may prompt the redistribution of the choroidal blood flow by the PRP, although there is no direct relationship with the vision change, but the safety of the retinal metabolism is ensured. Both the retina structure and function provided by the mfERG and the OCT examination have a certain effect on the visual prognosis of the eyes of the diabetic retinopathy after the PRP operation. Among them, the amplitude of the multi-focal electroretinogram and the central concave IS/ OS continuity are the most valuable prediction indexes.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R587.1;R774.1

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